HOIL-1 ubiquitin ligase activity targets unbranched glucosaccharides and is required to prevent polyglucosan accumulation.

HOIL-1, a component of the linear ubiquitin chain assembly complex (LUBAC), ubiquitylates serine and threonine residues in proteins by esterification. Here, we report that mice expressing an E3 ligase-inactive HOIL-1[C458S] mutant accumulate polyglucosan in brain, heart and other organs, indicating that HOIL-1's E3 ligase activity is essential to prevent these toxic polysaccharide deposits from accumulating. We found that HOIL-1 monoubiquitylates glycogen and α1:4-linked maltoheptaose in vitro and identify the C6 hydroxyl moiety of glucose as the site of ester-linked ubiquitylation. The monoubiquitylation of maltoheptaose was accelerated > 100-fold by the interaction of Met1-linked or Lys63-linked ubiquitin oligomers with the RBR domain of HOIL-1. HOIL-1 also transferred pre-formed ubiquitin oligomers to maltoheptaose en bloc, producing polyubiquitylated maltoheptaose in one catalytic step. The Sharpin and HOIP components of LUBAC, but not HOIL-1, bound to unbranched and infrequently branched glucose polymers in vitro, but not to highly branched mammalian glycogen, suggesting a potential function in targeting HOIL-1 to unbranched glucosaccharides in cells. We suggest that monoubiquitylation of unbranched glucosaccharides may initiate their removal from cells, preventing precipitation as polyglucosan.

ALPK1 mutants causing ROSAH syndrome or Spiradenoma are activated by human nucleotide sugars.

The atypical protein kinase ALPK1 is activated by the bacterial nucleotide sugar ADP-heptose and phosphorylates TIFA to switch on a signaling pathway that combats microbial infection. In contrast, ALPK1 mutations cause two human diseases: the ALPK1[T237M] and ALPK1[Y254C] mutations underlie ROSAH syndrome (retinal dystrophy, optic nerve oedema, splenomegaly, anhidrosis, and migraine headache), while the ALPK1[V1092A] mutation accounts for 45% of spiradenoma and 30% of spiradenocarcinoma cases studied. In this study, we demonstrate that unlike wild-type (WT) ALPK1, the disease-causing ALPK1 mutants trigger the TIFA-dependent activation of an NF-κB/activator protein 1 reporter gene in the absence of ADP-heptose, which can be suppressed by either of two additional mutations in the ADP-heptose binding site that prevent the activation of WT ALPK1 by ADP-heptose. These observations are explained by our key finding that although ALPK1[T237M] and ALPK1[V1092A] are activated by bacterial ADP-heptose, they can also be activated by nucleotide sugars present in human cells (UDP-mannose, ADP-ribose, and cyclic ADP-ribose) which can be prevented by disruption of the ADP-heptose binding site. The ALPK1[V1092A] mutant was also activated by GDP-mannose, which did not activate ALPK1[T237M]. These are new examples of disease-causing mutations permitting the allosteric activation of an enzyme by endogenous molecules that the WT enzyme does not respond to. We propose that the loss of the specificity of ALPK1 for bacterial ADP-heptose underlies ROSAH syndrome and spiradenoma/spiradenocarcinoma caused by ALPK1 mutation.

Association of serum biomarkers with radiographic knee osteoarthritis, knee pain and function in a young, male, trauma-exposed population - Findings from the ADVANCE study.

OBJECTIVE: The ArmeD SerVices TrAuma RehabilitatioN OutComE (ADVANCE) study is investigating long-term combat-injury outcomes; this sub-study aims to understand the association of osteoarthritis (OA) biomarkers with knee radiographic OA (rOA), pain and function in this high-risk population for post-traumatic OA. DESIGN: ADVANCE compares combat-injured participants with age, rank, deployment and job-role frequency-matched uninjured participants. Post-injury immunoassay-measured serum biomarkers, knee radiographs, Knee Injury and Osteoarthritis Outcome Scale, and six-minute walk tests are reported. The primary analysis, adjusted for age, body mass, socioeconomic status, and ethnicity, was to determine any differences in biomarkers between those with/without combat injury, rOA and pain. Secondary analyses were performed to compare post-traumatic/idiopathic OA, painful/painfree rOA and injury patterns. RESULTS: A total of 1145 male participants were recruited, aged 34.1 ± 5.4, 8.9 ± 2.2 years post-injury (n = 579 trauma-exposed, of which, traumatic-amputation n = 161) or deployment (n = 566 matched). Cartilage oligomeric matrix protein (COMP) was significantly higher in the combat-injured group compared to uninjured (p = 0.01). Notably, COMP was significantly lower in the traumatic-amputation group compared to non-amputees (p < 0.001), decreasing relative to number of amputations (p < 0.001). Leptin was higher (p = 0.005) and adiponectin lower (p = 0.017) in those with v without knee pain, associated with an increased risk of 22% and 17% for pain, and 46% and 34% for painful rOA, respectively. There were no significant differences between trauma-exposed and unexposed participants with rOA. CONCLUSIONS: The most notable findings of this large, unique study are the similarities between those with rOA regardless of trauma-exposure, the injury-pattern and traumatic-amputation-associated differences in COMP, and the relationship between adipokines and pain.

Acetylcholine, Fatty Acids, and Lipid Mediators Are Linked to COVID-19 Severity.

Lipid and cholinergic mediators are inflammatory regulators, but their role in the immunopathology of COVID-19 is still unclear. Here, we used human blood and tracheal aspirate (TA) to investigate whether acetylcholine (Ach), fatty acids (FAs), and their derived lipid mediators (LMs) are associated with COVID-19 severity. First, we analyzed the perturbation profile induced by SARS-CoV-2 infection in the transcriptional profile of genes related to the ACh and FA/LM pathways. Blood and TA were used for metabolomic and lipidomic analyses and for quantification of leukocytes, cytokines, and ACh. Differential expression and coexpression gene network data revealed a unique transcriptional profile associated with ACh and FA/LM production, release, and cellular signaling. Transcriptomic data were corroborated by laboratory findings: SARS-CoV-2 infection increased plasma and TA levels of arachidonic acid, 5-hydroxy-6E,8Z,11Z,14Z-eicosatetraenoic acid, 11-hydroxy-5Z,8Z,12E,14Z-eicosatetraenoic acid, and ACh. TA samples also exhibited high levels of PGE2, thromboxane B2, 12-oxo-5Z,8Z,10E,14Z-eicosatetraenoic acid, and 6-trans-leukotriene B4 Bioinformatics and experimental approaches demonstrated robust correlation between transcriptional profile in Ach and FA/LM pathways and parameters of severe COVID-19. As expected, the increased neutrophil-to-lymphocyte ratio, neutrophil counts, and cytokine levels (IL-6, IL-10, IL-1ß, and IL-8) correlated with worse clinical scores. Glucocorticoids protected severe and critical patients and correlated with reduced Ach levels in plasma and TA samples. We demonstrated that pulmonary and systemic hyperinflammation in severe COVID-19 are associated with high levels of Ach and FA/LM. Glucocorticoids favored the survival of patients with severe/critical disease, and this effect was associated with a reduction in ACh levels.

Effects of physical activity on depressive symptoms in older caregivers: The IMPACCT randomized controlled trial.

OBJECTIVES: Physical activity (PA) can reduce depressive symptoms but has not been tested amongst depressed older caregivers and their care-recipients. The aim of this single-blind randomized controlled trial was to investigate the effect of a 6-month tailored PA program on depressive symptoms in older caregivers. METHOD: Caregivers were included if they had scores of ≥5 on the 15-item geriatric depression scale (GDS-15). Care-recipients could have any type of physical, mental or cognitive condition requiring support. The PA intervention group completed an individualized program based on the Otago-Plus Exercise Program. The primary outcome was improvement in depressive symptoms in caregivers measured at six and 12 months. RESULTS: Two hundred and twelve participants (91 dyads and 30 caregivers only) were randomized using a 3:3:1 ratio to PA intervention, social-control, and usual-care control groups. There were no significant differences in depressive symptoms of the caregivers between the three groups at 6 months or 12 months. However, more than 50% of caregivers in all three groups no longer had a GDS-15 score ≥5 at 6 months. Further analysis revealed that caregivers in the PA group caring for someone with a standardised mini-mental state examination (SMMSE) score ≥24 had significantly less depressive symptoms than those caring for someone with a SMMSE score <24 compared with social-control (p < 0.02) and usual-care groups (p < 0.02). CONCLUSIONS: A PA intervention may be beneficial for some caregivers in reducing symptoms of depression but may not be as beneficial to caregivers of people living with cognitive impairment.

Pain after combat injury in male UK military personnel deployed to Afghanistan.

BACKGROUND: Chronic pain after injury poses a serious health burden. As a result of advances in medical technology, ever more military personnel survive severe combat injuries, but long-term pain outcomes are unknown. We aimed to assess rates of pain in a representative sample of UK military personnel with and without combat injuries. METHODS: We used data from the ADVANCE cohort study (ISRCTN57285353). Individuals deployed as UK armed forces to Afghanistan were recruited to include those with physical combat injuries, and a frequency-matched uninjured comparison group. Participants completed self-reported questionnaires, including 'overall' pain intensity and self-assessment of post-traumatic stress disorder, anxiety, and depression. RESULTS: A total of 579 participants with combat injury, including 161 with amputations, and 565 uninjured participants were included in the analysis (median 8 yr since injury/deployment). Frequency of moderate or severe pain was 18% (n=202), and was higher in the injured group (n=140, 24%) compared with the uninjured group (n=62, 11%, relative risk: 1.1, 95% confidence interval [CI]: 1.0-1.2, P<0.001), and lower in the amputation injury subgroup (n=31, 19%) compared with the non-amputation injury subgroup (n=109, 26%, relative risk: 0.9, 95% CI: 0.9-1.0, P=0.034). Presence of at least moderate pain was associated with higher rates of post-traumatic stress (RR: 3.7, 95% CI: 2.7-5.0), anxiety (RR: 3.2, 95% CI: 2.4-4.3), and depression (RR: 3.4, 95% CI: 2.7-4.5) after accounting for injury. CONCLUSION: Combat injury, but not amputation, was associated with a higher frequency of moderate to severe pain intensity in this cohort, and pain was associated with adverse mental health outcomes.

Activity-based E3 ligase profiling uncovers an E3 ligase with esterification activity.

Ubiquitination is initiated by transfer of ubiquitin (Ub) from a ubiquitin-activating enzyme (E1) to a ubiquitin-conjugating enzyme (E2), producing a covalently linked intermediate (E2-Ub) 1 . Ubiquitin ligases (E3s) of the 'really interesting new gene' (RING) class recruit E2-Ub via their RING domain and then mediate direct transfer of ubiquitin to substrates 2 . By contrast, 'homologous to E6-AP carboxy terminus' (HECT) E3 ligases undergo a catalytic cysteine-dependent transthiolation reaction with E2-Ub, forming a covalent E3-Ub intermediate3,4. Additionally, RING-between-RING (RBR) E3 ligases have a canonical RING domain that is linked to an ancillary domain. This ancillary domain contains a catalytic cysteine that enables a hybrid RING-HECT mechanism 5 . Ubiquitination is typically considered a post-translational modification of lysine residues, as there are no known human E3 ligases with non-lysine activity. Here we perform activity-based protein profiling of HECT or RBR-like E3 ligases and identify the neuron-associated E3 ligase MYCBP2 (also known as PHR1) as the apparent single member of a class of RING-linked E3 ligase with esterification activity and intrinsic selectivity for threonine over serine. MYCBP2 contains two essential catalytic cysteine residues that relay ubiquitin to its substrate via thioester intermediates. Crystallographic characterization of this class of E3 ligase, which we designate RING-Cys-relay (RCR), provides insights into its mechanism and threonine selectivity. These findings implicate non-lysine ubiquitination in cellular regulation of higher eukaryotes and suggest that E3 enzymes have an unappreciated mechanistic diversity.

Intra- and Inter-Rater Reliability of Linear and Nonlinear Measures of Short-Term Heart Rate Variability Following Combat-Related Traumatic Injury.

BACKGROUND: Heart rate variability (HRV) is a marker of autonomic function. However, the reliability of short-term HRV measurement in individuals with combat-related traumatic injury (CRTI) remains undetermined. METHODS: An intra- and inter-rater reliability study was conducted using a subsample (n = 35) of British servicemen with CRTI enrolled in the ongoing ADVANCE study. A five-minute epoch of single-lead electrocardiogram data collected during spontaneous breathing was used to measure HRV. HRV analyses were independently performed by two examiners using Kubios. Intraclass correlation coefficient (ICC), standard error of measurement (SEM), minimum detectable change (MDC), and coefficient of variance were calculated for linear [root mean square of successive difference (RMSSD), standard deviation of NN interval, low-frequency, high-frequency, total power] and nonlinear (SD1-2, acceleration and deceleration capacities, sample entropy) measures. Bland-Altman %plots were used to assess bias in intra- and inter-rater HRV data. RESULTS: The mean age of participants was 39.3 ± 6.3 years. An excellent ICC score of 0.9998 (95% CI 0.9997, 0.9999) was observed for intra-rater analyses of RMSSD, and similar excellent ICC scores were seen for all other HRV measures. The inter-rater reliability analyses produced an excellent ICC score (range 0.97-1.00). Comparatively, frequency-domain measures produced higher MDC% and SEM% scores than time-domain and nonlinear measures in both inter- and intra-rater analyses. The Bland-Altman plots revealed relatively higher bias for frequency-domain and nonlinear measures than time-domain measures. CONCLUSION: ECG-related short-term HRV measures were reliable in injured servicemen under spontaneous breathing. However, the reliability appeared better with the time-domain measure than frequency-domain and nonlinear measures in this sample.

Level of perceived social support, and associated factors, in combat-exposed (ex-)military personnel: a systematic review and meta-analysis.

PURPOSE: Combat deployment increases exposure to potentially traumatic events. Perceived social support (PSS) may promote health and recovery from combat trauma. This systematic review and meta-analysis aimed to synthesize studies investigating the level of PSS and associated factors among (ex-)military personnel who served in the Iraq/Afghanistan conflicts. METHODS: Five electronic databases were searched in August 2023 and searches were restricted to the beginning of the Iraq/Afghanistan conflicts in 2001. The search was conducted according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. A quality assessment was carried out, and a meta-analysis and narrative synthesis were performed. RESULTS: In total, 35 papers consisting of 19,073 participants were included. Of these, 31 studies were conducted in the United States (US) and 23 were cross-sectional. The pooled mean PSS score was 54.40 (95% CI: 51.78 to 57.01). Samples with probable post-traumatic stress disorder had a lower mean PSS score (44.40, 95% CI: 39.10 to 49.70). Approximately half of the included studies (n = 19) investigated mental health in relation to PSS, whilst only four explored physical health. The most frequently reported risk factors for low PSS included post-traumatic stress disorder, depression and anxiety, whilst post-traumatic growth and unit support were protective factors. CONCLUSION: Higher levels of PSS were generally associated with more positive psychosocial and mental health-related outcomes following deployment. PSS should be targeted in psychosocial interventions and education programmes. Future research should investigate PSS in (ex-)military personnel across other countries and cultures, based on the lack of studies that focused on PSS in countries outside of the US.

Deubiquitinating enzyme amino acid profiling reveals a class of ubiquitin esterases.

The reversibility of ubiquitination by the action of deubiquitinating enzymes (DUBs) serves as an important regulatory layer within the ubiquitin system. Approximately 100 DUBs are encoded by the human genome, and many have been implicated with pathologies, including neurodegeneration and cancer. Non-lysine ubiquitination is chemically distinct, and its physiological importance is emerging. Here, we couple chemically and chemoenzymatically synthesized ubiquitinated lysine and threonine model substrates to a mass spectrometry-based DUB assay. Using this platform, we profile two-thirds of known catalytically active DUBs for threonine esterase and lysine isopeptidase activity and find that most DUBs demonstrate dual selectivity. However, with two anomalous exceptions, the ovarian tumor domain DUB class demonstrates specific (iso)peptidase activity. Strikingly, we find the Machado-Joseph disease (MJD) class to be unappreciated non-lysine DUBs with highly specific ubiquitin esterase activity rivaling the efficiency of the most active isopeptidases. Esterase activity is dependent on the canonical catalytic triad, but proximal hydrophobic residues appear to be general determinants of non-lysine activity. Our findings also suggest that ubiquitin esters have appreciable cellular stability and that non-lysine ubiquitination is an integral component of the ubiquitin system. Its regulatory sophistication is likely to rival that of canonical ubiquitination.

The effects of music-based interventions on behavioural and psychological symptoms of people living with dementia: a systematic review and network meta-analysis protocol.

OBJECTIVES: People living with dementia often experience behavioural and psychological symptoms of dementia (BPSD), which severely affect their well-being during the course of the disease. Particularly for BPSD outcomes, there is a high demand for increasing the evidence-based knowledge of non-pharmacological approaches, such as music-based interventions. Although previous reviews emphasize the potential effects of music-based interventions in people with dementia, they cover a wide range of different interventions and outcomes. METHOD: Therefore, this systematic review (SR) and network meta-analysis (NMA) aims to not only investigate the efficacy of music-based interventions on BPSD, but also to compare the impact of different types of music-based interventions on outcomes. Preferred reporting items for SR and meta-analysis protocols (PRISMA-P) and the PRISMA NMA extension were followed. Several databases will be searched from inception to the date the search will be performed, for relevant randomized or non-randomized controlled trials comparing a music-based intervention with treatment as usual, active controls, or another music-based intervention. Multivariate pairwise meta-analyses will be conducted for each outcome. NMA based on a frequentist random-effects model will be used to estimate the comparative effects of each type of music-based intervention and related components across outcomes. Heterogeneity will be investigated by meta-regression models. CONCLUSION: Based on our knowledge, this may be the first SR and NMA study to compare the efficacy of different types of music-based interventions. In addition, combined with our multivariate analysis approach, it will allow us to identify potential effect modifiers in music-based intervention for treating BPSD.

Lifestyle Dimensions of Public Safety Personnel Families: There's No Life Like It.

PURPOSE: The nature and cumulative occupational demands imposed on families of public safety personnel (PSP) are substantial, in many cases non-negotiable, and distinct from the general population accentuating risk factors for family well-being. Despite this reality, the contributions of PSP families are not well understood, and a conceptual framework is needed. The aim of this paper is to summarize contextual factors (lifestyle dimensions) that shape the lives of PSP families; factors supported in the existing, albeit limited, body of research. METHODS: Grounded in the interpretive/constructivist paradigm, a synthesis was central to understanding the lived experiences of PSP families. An interdisciplinary research team engaged in an iterative process of framework analysis to capture the variability and complexity of PSP family life and distilled the overarching lifestyle dimensions. RESULTS: Three lifestyle dimensions-logistics, risks, and identities-emerged from contextual factors and represent distinct aspects of PSP family life. PSP families play a crucial role in that their capacity to accommodate the lifestyle dimensions (i.e., logistics, risks, and identities), without which the PSP could not meet the demands of the profession. CONCLUSION: Promoting awareness of these dimensions and their consequent demands underscores the cumulative demands that put PSP families at risk. Responses from governments, public safety organizations, and communities are required to help PSP families manage non-negotiable elements of the public safety occupation that spill over into family life over which they have no control.

Exploring the Occupational Lifestyle Experiences of the Families of Public Safety Personnel.

PURPOSE: Public safety personnel, including first responders, are regularly exposed to physical, social, and psychological risks and occupational requirements. These risks and requirements extend beyond the employee and may also impact the families (for example, work-family conflict, compassion fatigue). Despite recent attention directed at the population's wellness, considerably less attention is directed towards the family. This review investigates how the risks and requirements associated with these occupations affect families' lives and experiences, and correspondingly, how families respond and adapt to these risks. METHODS: In the current qualitative review, we sought to identify and describe the lifestyle experiences of public safety families as they navigate the occupational risks and requirements of public safety work. The inclusion criteria resulted in an analysis of 18 articles, representing only police (n = 11), paramedics (n = 7), and firefighting (n = 10) sectors. RESULTS: We identified and described the experiences of public safety families both by occupation and familial role. Shared familial themes across occupational groups included 'Worry', 'Communication', 'Where do I turn', 'Are they okay', 'Serving alongside', and '(Over)Protective'. However, distinct themes also emerged between different occupational groups and family configurations. Themes prevalent amongst primarily children of police included: 'Worry', 'Let's Laugh Instead', '(Over)Protective', and 'I'm not the Police, my Parent is!'. Experiences differed if the family contained on serving public safety personnel or multiple. CONCLUSION: We identified the shared and unique occupational experiences of public safety families. This review normalizes these experiences and emphasizes the need to develop initiatives to improve the well-being of families and safety employees.

Validity of Ultra-Short-Term Heart Rate Variability Derived from Femoral Arterial Pulse Waveform in a British Military Cohort.

Various non-electrocardiogram (ECG) based methods are considered reliable sources of heart rate variability (HRV) measurement. However, the ultra-short recording of a femoral arterial waveform has never been validated against the gold-standard ECG-based 300s HRV and was the aim of this study.A validity study was conducted using a sample from the first follow-up of the longitudinal ADVANCE study UK. The participants were adult servicemen (n = 100); similar in age, rank, and deployment period (Afghanistan 2003-2014). The femoral arterial waveforms (14s) from the pulse wave velocity (PWV) assessment, and ECG (300s) were recorded at rest in the supine position using the Vicorder™ and Bittium Faros™ devices, respectively, in the same session. HRV analysis was performed using Kubios Premium. Resting heart rate (HR) and root mean square of successive differences (RMSSD) were reported. The Bland-Altman %plots were constructed to explore the PWV-ECG agreement in HRV measurement. A further exploratory analysis was conducted across methods and durations.The participants' mean age was 38.0 ± 5.3 years. Both PWV-derived HR (r = 0.85) and RMSSD (rs=0.84) showed strong correlations with their 300s-ECG counterparts (p < 0.001). Mean HR was significantly higher with ECG than PWV (mean bias: -12.71 ± 7.73%, 95%CI: -14.25%, -11.18%). In contrast, the difference in RMSSD between the two methods was non-significant [mean bias: -2.90 ± 37.82% (95%CI: -10.40%, 4.60%)] indicating good agreement. An exploratory analysis of 14s ECG-vs-300s ECG measurement revealed strong agreement in both RMSSD and HR.The 14s PWV-derived RMSSD strongly agrees with the gold-standard (300s-ECG-based) RMSSD at rest. Conversely, HR appears method sensitive.

Post-traumatic growth amongst UK armed forces personnel who were deployed to Afghanistan and the role of combat injury, mental health and pain: the ADVANCE cohort study.

BACKGROUND: Post-traumatic growth (PTG) is a positive psychological consequence of trauma. The aims of this study were to investigate whether combat injury was associated with deployment-related PTG in a cohort of UK military personnel who were deployed to Afghanistan, and whether post-traumatic stress disorder (PTSD), depression and pain mediate this relationship. METHODS: 521 physically injured (n = 138 amputation; n = 383 non-amputation injury) and 514 frequency-matched uninjured personnel completed questionnaires including the deployment-related Post-Traumatic Growth Inventory (DPTGI). DPTGI scores were categorised into tertiles of: no/low (score 0-20), moderate (score 21-34) or a large (35-63) degree of deployment-related PTG. Analysis was completed using generalised structural equation modelling. RESULTS: A large degree of PTG was reported by 28.0% (n = 140) of the uninjured group, 36.9% (n = 196) of the overall injured group, 45.4% (n = 62) of amputee and 34.1% (n = 134) of the non-amputee injured subgroups. Combat injury had a direct effect on reporting a large degree of PTG [Relative risk ratio (RRR) 1.59 (95% confidence interval (CI) 1.17-2.17)] compared to sustaining no injury. Amputation injuries also had a significant direct effect [RRR 2.18 (95% CI 1.24-3.75)], but non-amputation injuries did not [RRR 1.35 (95% CI 0.92-1.93)]. PTSD, depression and pain partially mediate this relationship, though mediation differed depending on the injury subtype. PTSD had a curvilinear relationship with PTG, whilst depression had a negative association and pain had a positive association. CONCLUSIONS: Combat injury, in particular injury resulting in traumatic amputation, is associated with reporting a large degree of PTG.

Relationship between combat-related traumatic injury and its severity to predicted cardiovascular disease risk: ADVANCE cohort study.

BACKGROUND: This study investigated the relationship between combat-related traumatic injury (CRTI) and its severity and predicted cardiovascular disease (CVD) risk. MATERIAL AND METHODS: This was an analysis of comparative 10-year predicted CVD risk (myocardial infarction, stroke or CVD-death) using the QRISK®3 scoring-system among adults recruited into the Armed Services Trauma Rehabilitation Outcome (ADVANCE) cohort study. Participants with CRTI were compared to uninjured servicemen frequency-matched by age, sex, rank, deployment (Afghanistan 2003-2014) and role. Injury severity was quantified using the New Injury Severity Score (NISS). RESULTS: One thousand one hundred forty four adult combat veterans were recruited, consisting of 579 injured (161 amputees) and 565 uninjured men of similar age ethnicity and time from deployment/injury. Significant mental illness (8.5% vs 4.4%; p = 0.006) and erectile dysfunction (11.6% vs 5.8%; p < 0.001) was more common, body mass index (28.1 ± 3.9 vs 27.4 ± 3.4 kg/m2; p = 0.001) higher and systolic blood pressure variability (median [IQR]) (1.7 [1.2-3.0] vs 2.1 [1.2-3.5] mmHg; p = 0.008) lower among the injured versus uninjured respectively. The relative risk (RR) of predicted CVD (versus the population expected risk) was higher (RR:1.67 [IQR 1.16-2.48]) among the injured amputees versus the injured non-amputees (RR:1.60 [1.13-2.43]) and uninjured groups (RR:1.52 [1.12-2.34]; overall p = 0.015). After adjustment for confounders CRTI, worsening injury severity (higher NISS, blast and traumatic amputation) were independently associated with QRISK®3 scores. CONCLUSION: CRTI and its worsening severity were independently associated with increased predicted 10-year CVD risk.

Attitudes towards dementia among Chinese adults aged 50 years and older: a comparative study of immigrants living in Melbourne and nonimmigrants living in Beijing.

OBJECTIVES: This study investigated attitudes towards dementia among Chinese immigrants aged 50 years and over living in Australia and compares these attitudes with those of individuals living in mainland China. It aimed to better understand what older Chinese adults think about dementia and to inform the development of tailored dementia-related services for this group of people. DESIGN: A qualitative design involving individual interviews was employed in this study. PARTICIPANTS: Forty-six participants were recruited: 21 in Melbourne and 25 in Beijing. All interviewees were born in mainland China, were community-dwelling, and did not have a dementia diagnosis. MEASUREMENTS: The tripartite model of attitudes was used to guide the semi-structured interview design and report the results. Thematic qualitative analysis was employed. RESULTS: In both groups, most participants held negative feelings, stigmatized views and negative stereotypes of dementia. However, most participants expressed a willingness to help individuals living with dementia. Regarding dementia care, nearly all participants preferred home care but thought formal care would become the mainstream form of care in the future. Fewer Melbourne participants expressed concerns regarding developing dementia, were interested in dementia, or perceived a need for dementia-related educational activities. Melbourne participants also reported more avoidant responses to dementia or individuals living with dementia. CONCLUSION: This study carefully compares attitudes towards dementia between older Chinese immigrants in Melbourne and older Chinese adults in Beijing. Similarities and differences were observed between these two groups. Dementia-related service providers should consider the sociocultural changes and migration-related barriers experienced by Chinese immigrants.

Anger Among UK Ex-Service Military Personnel During the COVID-19 Pandemic.

ABSTRACT: Military service and ex-service personnel commonly experience difficulties with anger. The COVID-19 pandemic had several negative consequences upon social, economic, and health factors that influence anger. This study aimed to explore 1) levels of anger in an ex-serving military cohort during the COVID-19 pandemic; 2) self-reported changes in anger compared with prepandemic levels; and 3) identify sociodemographic characteristics, military characteristics, COVID-19 experiences, and COVID-19 stressors associated with anger. UK ex-service personnel ( n = 1499) completed the Dimensions of Anger Reactions 5-item measure within an existing cohort study. Overall, 14.4% reported significant difficulties with anger, and 24.8% reported their anger worsened during the pandemic. Anger was associated with factors such as financial difficulties, extra/new caring responsibilities, and COVID-19 bereavement. Endorsing more COVID-19 stressors was associated with higher odds of anger difficulties. This study highlights the impact of the pandemic on ex-service personnel, including a strain on family/social relationships and financial hardship, which affected anger.

Gender differences in structural and attitudinal barriers to mental healthcare in UK Armed Forces personnel and veterans with self-reported mental health problems.

PURPOSE: Structural and attitudinal barriers often hinder treatment-seeking for mental health problems among members of the Armed Forces. However, little is known about potential gender differences in structural and attitudinal barriers among members of the UK Armed Forces. The current study aimed to explore how men and women differ in terms of these barriers to care among a sample of UK Armed Forces personnel and veterans with self-reported mental health problems. METHODS: Currently serving and ex-serving members of the UK Armed Forces who self-reported a mental health problem were invited to participate in a semi-structured phone interview on mental health and treatment-seeking. The final sample included 1448 participants (1229 men and 219 women). All participants reported on their current mental health, public stigma, self-stigma, and barriers to mental healthcare. RESULTS: Overall, men and women reported similar levels of both structural and attitudinal barriers, with no significant differences detected. The highest scores for both men and women were observed in attitudinal barriers relating to self-stigma domains, which encapsulate internalised attitudes and beliefs about mental illness and treatment. CONCLUSIONS: Findings suggest that anti-stigma campaigns can be targeted simultaneously at both men and women within the Armed Forces. In particular, targeting self-stigma may be beneficial for health promotion campaigns.

Problem drinking recognition among UK military personnel: prevalence and associations.

PURPOSE: Despite the higher prevalence of problem drinking in the UK military compared to the general population, problem recognition appears to be low, and little is known about which groups are more likely to recognise a problem. This study examined prevalence of problem drinking recognition and its associations. METHODS: We analysed data from 6400 regular serving and ex-serving personnel, collected in phase 3 (2014-2016) of the King's Centre for Military Health Research cohort study. MEASUREMENTS: Participants provided sociodemographic, military, health and impairment, life experiences, problem drinking, and problem recognition information. Problem drinking was categorised as scores ≥ 16 in the AUDIT questionnaire. Associations with problem recognition were examined with weighted logistic regressions. FINDINGS: Among personnel meeting criteria for problem drinking, 49% recognised the problem. Recognition was most strongly associated (ORs ≥ 2.50) with experiencing probable PTSD (AOR = 2.86, 95% CI = 1.64-5.07), social impairment due to physical or mental health problems (AOR = 2.69, 95% CI = 1.51-4.79), adverse life events (AOR = 2.84, 95% CI = 1.70-4.75), ever being arrested (AOR = 2.99, CI = 1.43-6.25) and reporting symptoms of alcohol dependence (AOR = 3.68, 95% CI = 2.33-5.82). To a lesser extent, recognition was also statistically significantly associated with experiencing psychosomatic symptoms, feeling less healthy, probable common mental health disorders, and increased scores on the AUDIT. CONCLUSION: Half of UK military personnel experiencing problem drinking does not self-report their drinking behaviour as problematic. Greater problem drinking severity, poorer mental or physical health, and negative life experiences facilitate problem recognition.